Considerable evidence has been accumulated which indicates that the ultimate carcinogens of polycyclic aromatic hydrocarbons (PAHs) are diol-epoxides. In order to gain additional insight into the mechanism of activation of PAH's we propose to study the metabolism of 3-methylcholanthrene (3-MC). No diols of this compound have yet been isolated which would support the diol-epoxide theory. The aims of the proposed research are to (1) identify all primary metabolites of 3-MC, (2) compare the primary metabolites of 3-MC to the known metabolities of other carcinogenic hydrocarbons and determine if a common pathway for activation exists, (3) compare the levels of the primary metabolites of 3-MC from the livers and lungs of susceptible and resistant strains of mice to establish if the formation of a certain metabolite is related to susceptibility, and (4) determine if there is a relationship between lung epoxide hydrase levels and susceptibility to lung tumor formation. Preliminary studies show that high pressure liquid chromatography provides an effective means of separating the metabolites of 3-MC. These investigations are designed to increase our understanding of the mechanism of metabolic activation in relation to chemical carcinogenesis.